Department of Periodontology, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
Graduate Institute of Dental Sciences, National Defense Medical Center, Taipei, Taiwan.
J Periodontol. 2023 Jul;94(7):905-918. doi: 10.1002/JPER.22-0535. Epub 2023 Mar 8.
Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti-inflammatory, and immunoregulatory properties. However, the therapeutic potential of silibinin for periodontitis has not been investigated.
The therapeutic effects of silibinin in ligation-induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS-stimulated HGFs and undifferentiated monocytes.
Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL-induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL-induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS-stimulated HGFs; significantly suppressed membrane-bound RANKL expression on LPS-stimulated HGFs; and significantly disrupted TRAP cell differentiation in the coculture system.
Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug-repurposing candidate for modulating alveolar bone destruction in periodontitis.
Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.
水飞蓟宾具有抗氧化、抗炎和免疫调节特性，表现出多种药理作用。然而，水飞蓟宾治疗牙周炎的潜力尚未得到研究。
采用生化、组织学和免疫组织化学方法研究水飞蓟宾在结扎诱导的实验性牙周炎中的治疗作用。通过 TRAP 染色、定量聚合酶链反应（qPCR）、陷窝形成和免疫印迹研究水飞蓟宾对 RAW264.7 细胞破骨细胞形成的影响。此外，通过 qPCR 和流式细胞术评估其对脂多糖（LPS）刺激的人牙龈成纤维细胞（HGFs）中炎症细胞因子产生、RANKL 表达和氧化应激的影响。建立共培养系统阐明水飞蓟宾对 LPS 刺激的 HGFs 与未分化单核细胞之间串扰的影响。
水飞蓟宾显著减少实验性牙周炎中的牙槽骨丢失，减轻牙龈炎症和 RANKL 表达，并降低牙龈组织中的 RANKL/骨保护素比值。体外结果表明，水飞蓟宾抑制 RANKL 诱导的 RAW264.7 细胞破骨细胞分化和功能，并通过核因子-κB 和丝裂原活化蛋白激酶信号通路抑制 RANKL 诱导的激活 T 细胞核因子 1（NFATc1）诱导和易位。水飞蓟宾降低 LPS 刺激的 HGFs 中炎症细胞因子水平和氧化应激产物；显著抑制 LPS 刺激的 HGFs 上膜结合 RANKL 的表达；并在共培养系统中显著破坏 TRAP 细胞分化。
水飞蓟宾通过抑制炎症刺激的 HGFs 中炎症和破骨细胞生成介质的表达，有效抑制实验性牙周炎中炎症诱导的骨丢失。总之，靶向介导成骨作用的炎症刺激的 HGF 可能将水飞蓟宾作为一种潜在的药物再利用候选物，用于调节牙周炎中的牙槽骨破坏。
水飞蓟宾通过抑制炎症刺激的 HGFs 中炎症和破骨细胞生成介质的表达，有效抑制实验性牙周炎中炎症诱导的骨丢失。
